Giovanna Zinzalla Project
Assistant Professor (Senior) in Chemical Biology
Centre for Advanced Cancer Therapies (ACT), Karolinska Institute, SE-17177 Stockholm, Sweden
Phone: +46 (0) 8524 81262 (office)
Mobile: +46 735 668336
Science for Life Laboratory
Alpha house, Level 5,
Rooms: A5590 (office), A5672 (laboratory)
171 65 Stockholm, Sweden
Science for Life Laboratory
171 21 Stockholm, Sweden
Chemistry To Understand and Manipulate Master Regulators of Transcription
The Zinzalla research group focuses on using chemical approaches to address fundamental questions in the biology of cancer and open doors to exciting new areas for cancer therapy. They apply a wide range of techniques, including chemical synthesis, biophysics and structural biology.
We focus, in particular, on the modulation of protein-protein interactions (PPIs) that regulate the signalling pathway of transcription factors (TFs) as TFs are the primary drivers of tumorigenesis. The modulation of Protein-Protein Interactions (PPIs) with synthetic agents has been proved to be a powerful approach to probe cellular functions, and PPIs are considered to be a gold mine of molecular targets for developing new and more-selective chemotherapeutic agents.
Currently the group is working on PPIs that control c-MYC transcriptional activation and on PPIs that are responsible for c-MYC transcriptional repression. c-MYC is a complex signalling pathway, which further understanding hold much promise to deliver the most powerful cancer therapies. Our objective is also to use these chemical agents to elucidate the interplay of c-MYC with other transcription factors that regulate the survival and growth of cancer cells, playing a key role in another complex aspect of tumor biology as cancer metabolism.
Areas of Expertise
Organic and Medicinal Chemistry, Biochemistry, Structural Biology, Biochemical and Biophysical Assays, Structure-Based Molecular Design, Protein-Protein Interactions, Drug Discovery, Cancer Research
- Dr Mark Bycroft, MRC LMB, Cambridge, UK
- Professor Jane Clarke, University of Cambridge, UK
- Professor Gerard Evan, University of Cambridge, UK
- Dr. Björn Windshügel, Fraunhofer Institute IME, Germany
- Professor Lars-Gunnar Larsson, Karolinska Institutet, Sweden
Dr Zinzalla obtained her first class honours Laurea in Chemistry (equivalent to MChem) from the University of Milan and carried out her PhD studies with Professor Stefano Maiorana and Dr Clara Baldoli also at the University of Milan. For her PhD research she was awarded the Young Researcher Award by the Italian Ministry of Education and Science. Her research focused on the development of metal complex conjugates of Peptide Nucleic Acids as novel biosensors, and she investigated novel traceless linkers for solid-phase synthesis of drug-like small molecules in collaboration with GlaxoSmithKline.
In 2004 she was awarded a Marie Curie EIF Postdoctoral Research Fellowship and appointed as Postdoctoral Research Assistant at the University of Cambridge with Professor Steven Ley. Here she initiated a new project focused on exploring the role of molecular diversity for drug discovery, with the design of natural product-like small molecules as novel therapeutic agents.
In June 2006 she joined the School of Pharmacy, University College London (UCL) (London, UK) as a Senior Research Fellow funded by Cancer Research UK (CR UK), within the CR UK Protein-Protein Interactions Drug Discovery Research Group. As co-PI of a CR UK Small Molecule Drug Discovery Initiative Programme she led research projects aimed at discovering PPI inhibitors of transcriptional factors such as Hypoxia Inducible Factor 1 (HIF-1) and Signal Transducer and Activator of Transcription 3 (STAT3).
Since January 2012 she has held a Forskare position as and a junior Group Leader at the Centre for Advanced Cancer Therapies (ACT), MTC Department. In January 2012 she took up the faculty position at Karolinska Institutet as Assistant Professor in Chemical Biology at MTC.
Targeting MYC: is it getting any easier?
Future Med Chem 2016 Oct;8(16):1899-1902
A New Way Forward in Cancer Drug Discovery: Inhibiting the SWI/SNF Chromatin Remodelling Complex.
Chembiochem 2016 Apr;17(8):677-82
Paving the way to targeting HECT ubiquitin ligases.
Future Med Chem 2015 ;7(16):2107-11
Targeting protein-protein interactions (PPIs) of transcription factors: Challenges of intrinsically disordered proteins (IDPs) and regions (IDRs).
Prog. Biophys. Mol. Biol. 2015 Oct;119(1):41-6
Tetracycline analogues with a selective inhibitory effect on HIF-1alpha
Bendiabdellah Y, Rahman, KM, Uranchimeg B, Nahar KS, Antonow D, Shoemaker R.H., Melillo G, Zinzalla G, Thurston, DE
Med. Chem. Commun., 2014,5, 923-926.
Understanding and Exploiting ProteinProtein Interactions as Drug Targets
October 2013, Future Medicine book series, Publisher: Future Science Group
Investigation of the protein alkylation sites of the STAT3:STAT3 inhibitor Stattic by mass spectrometry.
Bioorg. Med. Chem. Lett. 2013 Aug;23(16):4719-22
Observation of unphosphorylated STAT3 core protein binding to target dsDNA by PEMSA and X-ray crystallography.
FEBS Lett. 2013 Apr;587(7):833-9
Small-molecule inhibition of c-MYC:MAX leucine zipper formation is revealed by ion mobility mass spectrometry.
J. Am. Chem. Soc. 2012 Nov;134(47):19384-92
Molecular dynamics studies of the STAT3 homodimer:DNA complex: relationships between STAT3 mutations and protein-DNA recognition.
J Chem Inf Model 2012 May;52(5):1179-92
A novel small-molecule inhibitor of IL-6 signalling.
Bioorg. Med. Chem. Lett. 2010 Dec;20(23):7029-32
Facile nucleophilic substitution at the C3a tertiary carbon of the 3a-bromohexahydropyrrolo[2,3-b]indole scaffold.
Org. Biomol. Chem. 2010 Dec;8(23):5294-303
Facile oxidation of electron-poor benzo[b]thiophenes to the corresponding sulfones with an aqueous solution of H2O2 and P2O5.
Chem. Commun. (Camb.) 2010 Apr;46(13):2289-91
Targeting protein-protein interactions for therapeutic intervention: a challenge for the future.
Future Med Chem 2009 Apr;1(1):65-93
Natural-product-like spiroketals and fused bicyclic acetals as potential therapeutic agents for B-cell chronic lymphocytic leukaemia.
ChemMedChem 2008 Dec;3(12):1922-35
Chemical variation of natural-product-like scaffolds: design, synthesis, and biological activity of fused bicyclic acetal derivatives.
Angew. Chem. Int. Ed. Engl. 2007 ;46(14):2493-6
Chemical variation of natural product-like scaffolds: design and synthesis of spiroketal derivatives.
Org. Biomol. Chem. 2006 May;4(10):1977-2002
Synthesis of chiral chromium tricarbonyl labeled thymine PNA monomers via the Ugi reaction.
Org. Lett. 2002 Nov;4(24):4341-4
Bendiabdellah, Y.; Margalef-Villanueva, I.; Misale, A.; Nahar, K.; Haque, M.R.; Thurston, D.E.; Zinzalla, G.
One-pot synthesis of fused tetracyclic scaffolds via a Lewis acid promoted domino reaction of naphthoquinones
Synthesis 2011, 14, 2321
View the Abstract Online
Baldoli, C.; Giannini, C.; Licandro, E.; Maiorana, S.; Zinzalla, G.,
A Thymine-PNA monomer as new isocyanide component in the Ugi reaction: a direct entry to PNA dimers
Synlett, 2004, 6, 1044
View the Abstract Online